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Leptospirosis
Leptospiral Infection

Leptospirosis is an infectious disease which occurs in humans, rodents and other wild and domesticated species. 

Images

WIKIDATA, Public Domain
WIKIDATA, Public Domain
WIKIDATA, Public Domain
WIKIDATA, CC BY-SA 4.0
WIKIDATA, CC BY-SA 4.0

Presentation

There is a wide range of symptoms that can occur in humans who are affected by leptospirosis even though some people will be asymptomatic [8]. Since the disease is considered a biphasic disease it presents initially through flu-like symptoms including malaise, fever, chills, myalgia and headache.

The mild form of the disease is considered to be the first phase and will usually resolve after 3 to 7 days. If the disease progresses to the secondary stage, liver damage and jaundice can occur along with renal failure, lung infection, meningitis, and encephalitis.

General symptoms are:

  • Anorexia
  • Conjunctivitis
  • Cough
  • Pharyngitis
  • Diarrhea 
  • Fever
  • Headache
  • Myalgia
  • Nausea
  • Vomiting
  • Rash
  • Abdominal pain
  • Rigors

Immune System

  • Splenomegaly

    Splenomegaly and hepatomegaly are uncommon. This phase lasts 4 to 9 days, with recurrent chills and fever that often spikes to > 39° C. Defervescence follows. [merckmanuals.com]

    Ultrasound may reveal splenomegaly, hepatomegaly, or renal enlargement. A case-control study found that the kidneys of patients with confirmed leptospirosis were approximately 1.5 cm larger than control patients. [cancertherapyadvisor.com]

    Other signs include masculopapular skin rash, pharyngeal injection, lymphadenopathy, splenomegaly, hepatomegaly, and muscle tenderness. [scielo.br]

Entire Body System

  • Fever

    Weil disease; Icterohemorrhagic fever; Swineherd's disease; Rice-field fever; Cane-cutter fever; Swamp fever; Mud fever; Hemorrhagic jaundice; Stuttgart disease; Canicola fever Galloway RL, Stoddard RA, Schafer IJ. Leptospirosis. [nlm.nih.gov]

    This was also known as tibial fever. Autumn fever (Akiyami fever from the Japanese) Due to the periodicity in temperate climates. [dx.doi.org]

    Acute undifferentiated fever, i.e., acute fever without an obvious focus of infection, is the most common clinical presentation of both leptospirosis and scrub typhus ( 11 ). [doi.org]

    Yellow fever Relapsing fever Scrub typhus Dengue fever Legionnaires' disease Toxic shock syndrome Investigations The initial diagnosis of leptospirosis is based on clinical features. [patient.info]

  • Veterinarian

    If you have any questions regarding the vaccine, contact your equine veterinarian. [wagwalking.com]

    Dog owners should consult with their veterinarian about vaccinating their dogs against leptospirosis. Where can I get more information about leptospirosis? The U.S. [cdph.ca.gov]

    Leptospirosis vaccines may only protect dogs for six-to-eight months, so veterinarians in high risk areas recommend twice-yearly vaccination. [canismajor.com]

    If you think your pet may have leptospirosis, contact your veterinarian immediately. Your veterinarian can perform tests to determine whether or not your pet has the disease. [veterinarypartner.com]

    What Tests Will My Veterinarian Use To Diagnose Lepto In My Dog ? Like many infectious disease your veterinarian encounters, the initial blood analysis reports are rarely definitive for one certain disease. [2ndchance.info]

  • Chills

    Technical Information for Leptospirosis Clinical Features Symptoms of leptospirosis include fever, headache, chills, muscle aches, vomiting/diarrhea, cough, conjunctival suffusion, jaundice, and sometimes a rash. [cdc.gov]

    Leptospirosis Symptoms Chills Chills are feelings of coldness accompanied by shivering. They may arise with or without fever. Without fever, chills typically arise after exposure to a cold environment. [medicinenet.com]

    (with rigor) R50.9 ICD-10-CM Diagnosis Code R50.9 Fever, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Fever NOS Fever of unknown origin [FUO] Fever with chills Fever with rigors Hyperpyrexia NOS Persistent fever Pyrexia NOS mud [icd10data.com]

    His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. [ncbi.nlm.nih.gov]

  • Anemia

    After 9 days from the onset of the disease, the patient developed acute necrotizing pancreatitis, infected from the very beginning, associated with multiple organ failure, septic shock and severe anemia. [ncbi.nlm.nih.gov]

    Several studies have noted a high prevalence of anemia and other hematological abnormalities in patients with leptospirosis. [doi.org]

    Weil syndrome is a severe form with jaundice and usually azotemia, anemia, diminished consciousness, and sometimes hemorrhagic manifestations. [merckmanuals.com]

  • Rigor

    R50.9 ICD-10-CM Diagnosis Code R50.9 Fever, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Fever NOS Fever of unknown origin [FUO] Fever with chills Fever with rigors Hyperpyrexia NOS Persistent fever Pyrexia NOS mud A27.9 swamp [icd10data.com]

    General symptoms are: Anorexia Conjunctivitis Cough Pharyngitis Diarrhea Fever Headache Myalgia Nausea Vomiting Rash Abdominal pain Rigors After the initial seven to ten days following exposure, the microorganism related to the disease can be found in [symptoma.com]

    Although few rigorous studies have considered the environmental phase of infectious Leptospira bacteria, relevant observations about their presence and survival have been compiled since the beginning of the 20th century ( 30 ) and suggest that environmental [doi.org]

    In typical examples, fever rose to 37.8-38.4°C with severe rigors and hypotension, 4-5 h after the institution of intravenous penicillin therapy ( 37, 39 ). The mechanism of the JH reaction in leptospirosis is not established. [antimicrobe.org]

    It is characterized by sudden onset of the following: Fever (38-40°C) Rigors Headache, retro-orbital pain, photophobia Muscle pain localized to the calf and lumbar areas Conjunctival suffusion Dry cough Nausea and vomiting, diarrhea More severe disease [emedicine.medscape.com]

Gastrointestinal

  • Loss of Appetite

    See a GP if you might have been exposed to infected pee and you have: a very high temperature, or feel hot and shivery a headache feeling and being sick aching muscles and joints red eyes loss of appetite These are symptoms of leptospirosis. [nhs.uk]

    Firstly, the clinical symptoms can include lethargy (low energy), loss of appetite, red eyes, vomiting, diarrhea, increased urination. In the most severe cases Leptospirosis can result in liver and kidney failure, leading to death. [petdoctorx.com]

Liver, Gall & Pancreas

  • Jaundice

    Other symptoms may include: conjunctivitis, vomiting, diarrhea, stomach pain, jaundice, cough, and rarely a skin rash. [cdc.gov]

    About 10 to 15% of patients with Weil's disease become severely ill with: a 'flu-like illness, followed by, jaundice haemorrhage renal impairment The majority suffer a benign self-limiting illness without jaundice. [gpnotebook.co.uk]

    The flu-like illness may resolve without treatment but, in some cases, an immune phase follows with a return of fever, jaundice, red eyes, abdominal pain, diarrhoea, or a rash. [patient.info]

    The death rate is approximately 30 percent of the severely ill and jaundiced patients. Diagnosis is established by identification of the causative organism in urine or blood and by blood cultures on special media. [britannica.com]

Eyes

  • Conjunctival Injection

    All of the cases had fevers, headaches, conjunctival injections, and relative bradycardia. The pertinent laboratory findings included elevated C-reactive protein levels, elevated creatinine levels, and sterile pyuria. [ncbi.nlm.nih.gov]

    Conjunctival suffusion should be differentiated from conjunctival injection (nonuniform redness) or subconjunctival hemorrhages. Conjunctival suffusion and myalgias are considered pathognomonic of leptospirosis. [doi.org]

  • Eye Pain

    The headache in leptospirosis is characteristically located at the bilateral temporal regions, or frontal headache with throbbing pain, associated with pain behind the eyes and sensitivity to light. [en.wikipedia.org]

Musculoskeletal

  • Myalgia

    A 45-years-old male presented with 16 hours duration of myalgia, conjunctival suffusion, progressive flaccid quadriparesis, respiratory muscle weakness and dysphasia. [ncbi.nlm.nih.gov]

Skin

  • Skin Rash

    Skin rash, conjunctival suffusion, and subconjunctival hemorrhage led us to the diagnosis of leptospirosis and the microscopic agglutination test confirmed the diagnosis. [ncbi.nlm.nih.gov]

    Other symptoms may include: conjunctivitis, vomiting, diarrhea, stomach pain, jaundice, cough, and rarely a skin rash. [cdc.gov]

    Symptoms include sudden fever, headache, muscle pain, chills, red itchy eyes, difficulty urinating, a skin rash, nausea, vomiting, and diarrhea. [iamat.org]

  • Petechiae

    […] thirst and urination, may be indicative of chronic renal (kidney) failure, progressing to inability to urinate Rapid dehydration Vomiting, possibly with blood Diarrhea - with or without blood in stool Bloody vaginal discharge Dark red speckled gums ( petechiae [petmd.com]

    Meanwhile, in the lungs, petechiae or frank bleeding can be found at alveolar septum and spaces between alveoli. Leptospira can cause mild to severe kidney failure. [en.wikipedia.org]

    Freshly aborted foetuses often have petechiae on the skin and haemorrhages in kidney, lungs and liver. Straw coloured fluid is present in body cavities. [pigprogress.net]

    However, hemorrhagic manifestations, which are due to capillary injury and include epistaxis, hemoptysis, petechiae, purpura, and ecchymoses, then develop and rarely progress to subarachnoid, adrenal, or gastrointestinal hemorrhage. [merckmanuals.com]

Urogenital

  • Dark Urine

    His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. [ncbi.nlm.nih.gov]

Neurologic

  • Headache

    Technical Information for Leptospirosis Clinical Features Symptoms of leptospirosis include fever, headache, chills, muscle aches, vomiting/diarrhea, cough, conjunctival suffusion, jaundice, and sometimes a rash. [cdc.gov]

    The data taken into account include: age and sex of the patient, their home island, the consultation period and the results of leukocytes, platelets, CRP, creatinine and GGT tests combined with 2 major clinical signs, headache and conjunctival suffusion [ncbi.nlm.nih.gov]

  • Meningism

    About 10 percent of people with leptospirosis develop severe disease, including kidney or liver failure, meningitis, difficulty breathing, bleeding, and meningitis. Case fatality rate is 5 to 15% in cases with severe clinical illness. [cdc.gov]

    CASE PRESENTATION: Here we present one male patient with anicteric leptospirosis that manifested as neuroleptospirosis with aseptic meningitis, although he did not have impaired kidney function or thrombocytopenia. [ncbi.nlm.nih.gov]

    The signs and symptoms include an initial flu-like phase, followed by a second phase in which patients may develop meningitis, liver failure and renal failure. [icd9data.com]

  • Confusion

    A confusing array of laboratory tests is described for the detection of this spirochete and antibodies. The conventional tests include direct microscopy, culture and the most widely used reference standard method -the microscopic agglutination test. [ncbi.nlm.nih.gov]

    Less frequently, it can result in meningitis, liver and kidney dysfunction, pulmonary involvement, and mental confusion. Severe cases occur more commonly in older persons and can result in death. [dhs.wisconsin.gov]

  • Guillain-Barré Syndrome

    A variety of neurological complications can occur such as hemiplegia, transverse myelitis, and Guillain-Barré syndrome. [en.wikipedia.org]

    Isolated reports exist of leptospirosis causing radiculopathies, transverse myelitis, cranial nerve palsies and Guillain–Barré syndrome. 37 Cardiac abnormalities include myocarditis and pericarditis. 50, 51 Electrocardiographic abnormalities are frequent [dx.doi.org]

Workup

After the initial seven to ten days following exposure, the microorganism related to the disease can be found in fresh urine as well as in blood and cerebrospinal fluid [9]. 

During the workup for the disease diagnostic testing can include blood cultures and serum tests that will be tested against a panel of possible strains. Kidney function tests will also be done including blood urea nitrogen, and creatinine tests. Liver function tests will also be done. Diagnosis will then be confirmed through enzyme-linked immunosorbent assay (ELISA) tests and polymerase chain reaction (PCR).

Urine

  • Pyuria

    After standard antibiotic therapy and recovery from severe clinical illness, he developed unilateral orchitis with pyuria secondary to leptospirosis, a well-established complication in the veterinary literature, but of which we offer the first report [ncbi.nlm.nih.gov]

    Renal abnormalities include proteinuria, pyuria, hematuria, and azotemia. Hepatocellular damage is minimal, and healing is complete. Mortality is nil in anicteric patients. [merckmanuals.com]

    Urinalysis may reveal proteinuria, pyuria, and occasional microscopic hematuria[ 2 ]. Creatine kinase and serum amylase may also be elevated. [doi.org]

Serum

  • Neutrophilia

    The abovementioned factors along with neutrophilia and pulmonary opacity were used in the development of the score. [ncbi.nlm.nih.gov]

    Other laboratory abnormalities include anemia, thrombocytopenia, leucocytosis with neutrophilia and an increase in the level of creatinine phosphokinase (i.e. the MM fraction) [48]. [scielo.br]

  • Hyponatremia

    The simplified score with 7 variables was the summation of the odds ratio values as follows: hypotension 3, jaundice 2, muscle pain 2, AKI 1.5, low hemoglobin 3, hypokalemia with hyponatremia 3, and neutrophilia 1. [ncbi.nlm.nih.gov]

    In cases with more severe renal manifestations, serum creatinine is often elevated, and both hypokalemia and hyponatremia may be present[ 13 ]. [doi.org]

    Leptospirosis causes increased potassium excretion in the urine, which leads to a low potassium level in the blood (hypokalemia) and hyponatremia (low sodium level). [en.wikipedia.org]

  • Decreased Platelet Count

    The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. [ncbi.nlm.nih.gov]

Treatment

In mild cases of leptospirosis, antibiotics like amoxicillin, ampicillin, doxycycline, and penicillin G. are considered to be the most effective, but the use is still controversial. If the case proves to be more severe, cefotaxime or ceftriaxone should be prescribed [10].

Some serious cases that affect the kidneys and need dialysis may be treated with glucose and salt solution infusions in addition to the dialysis. Renal failure, high potassium levels, and other associated conditions will need their own treatment.

Prognosis

In the mild form, which accounts for 90 percent of the reported cases, leptospirosis is usually not fatal [7]. The mortality rate increases in the more severe form of the disease.

When the disease affects humans, the elderly community and people with compromised immune systems are most at risk in terms of mortality. These deaths usually occurs due to renal failure, acute respiratory distress syndrome, liver failure, meningitis and hemorrhage.

Etiology

Leptospirosis is caused by the Leptospira species which is a spirochaete bacterium. In the US and Canada there are about five serotypes of the bacterium that lead to disease. There are [2]:

  • Bratislava
  • Canicola
  • Grippotyphosa
  • Icterohaemorrahagiae
  • Pomona

Other than these serotypes there are a number of strains that are considered to be more lethal. Arguments over strain identification come about due to the nature of the species. Technologies, including polymerase chain reactions, which can help with strain identification.

The primary animal hosts are rates, moles, and mice, but any animal can carry and transmit the disease. This can include cows, dogs, hedgehogs, rabbits, raccoons, sheep, deer, opossums, skunks, and marine mammals. The bacteria and subsequent disease leptospirosis is transmitted via the urine or other bodily fluid of an infected animal. It can remain contagious as long as the fluid in question remains moist [3]. Secondary hosts, like humans, can also spread the disease after contracting it.

Epidemiology

The disease doesn’t seem to have a preference for gender, race, or age and can be contracted by anyone who comes into contact with the bacteria. There are more instances of the disease in tropical regions where there can be 10 to 100 reported cases in 100,000 population. Temperate regions can see much smaller numbers (0.02 in 100,000). Annually, there are between 7 and 10 million people affected by leptospirosis [4].

Pathophysiology

Leptospirosis is caused by the Leptospira species of bacteria which are coiled aerobic gram-negative organisms. They are able to burrow into a host’s tissue due to their hooked ends and paired axial flagella [5]. 

The most important source for the pathogens is the urinary shedding of infected animals. Humans become infected with the disease after coming into contact with infected urine or contaminated water, food, bedding, soil/mud, or aborted tissue from an infected animal. The bacteria can live for as long as 16 days in fresh water and for 24 days in soil if conditions are appropriate.

Occupations at risk include slaughterhouse workers, sewage workers, veterinarians, farmers, waste disposal facility workers and military personnel. Recreational activities such as swimming, windsurfing, kayaking or rowing may also result in contracting the disease from contaminated water or soil.

The disease can enter the host via:

  • Abrasions 
  • Animal bites
  • Inhalation of aerosolised body fluid
  • Mucous membranes or conjunctiva
  • Placenta during pregnancy

With leptospirosis, the most common finding is vasculitis of the capillaries which is seen in each affected organ system. This condition causes probably most of the clinical findings [6].

Prevention

Since this disease is contracted by coming into contact with infected animal body fluids, the best form of prevention is to avoid coming into contact with the bodily fluids of primary hosts. If dealing with these animals or any animal that might be infected, all surfaces should be thoroughly cleaned and sanitized. Gloves should also be worn at all times in order to avoid contact with contaminated surfaces or animals. If it’s possible that another animal, like a pet, came into contact with rodent droppings or urine, they should be monitored for symptoms.

Summary

Leptospirosis is an infectious disease that is caused by the pathogenic spirochetes of the genus Leptospira [1]. It is seen more often in tropical areas where the weather is warmer but, with an increase in global warming, the infectious disease is occurring more frequently than usual making it the most common zoonosis in the world. The only areas where no cases of leptospirosis are reported, are the Polar regions.

Humans that are affected by leptospirosis are considered to be accidental hosts in most cases and aren’t thought to be carriers of the Leptospira species. The animals that are mostly affected by this disorder are various mammals, reptiles, birds and amphibians. The humans who are accidentally contracting the disease do so when they come into contact with the body fluid of an infected animal or through exposure to contaminated soil or water.

Patient Information

Leptospirosis is a disease that mainly affects animals but can affect humans if they come into contact with the bodily fluid of an infected animal. If the disease progresses without treatment it can be fatal.

Most commonly, rodents carry the disease. Steering clear of these host animals and cleaning up after them if they get into your home is essential in preventing the spread of the disease.

If a human or animal does contract leptospirosis, it can be treated with antibiotics and has a high cure rate when caught in the mild state. While severe forms of the disease are rare, it can happen and lead to other problems like renal failure.

References

  1. Palaniappan RU, Ramanujam S, Chang YF. Leptospirosis: pathogenesis, immunity, and diagnosis. Curr Opin Infect Dis. Jun 2007;20(3):284-92. 
  2. Yang CW. Leptospirosis in Taiwan--an underestimated infectious disease. Chang Gung Med J. Mar-Apr 2007;30(2):109-15. 
  3. Radl C, Müller M, Revilla-Fernandez S, Karner-Zuser S, de Martin A, Schauer U, et al. Outbreak of leptospirosis among triathlon participants in Langau, Austria, 2010. Wien Klin Wochenschr. Dec 2011;123(23-24):751-5. 
  4. Gaynor K, Katz AR, Park SY, Nakata M, Clark TA, Effler PV. Leptospirosis on Oahu: an outbreak associated with flooding of a university campus. Am J Trop Med Hyg. May 2007;76(5):882-5. 
  5. Socolovschi C, Angelakis E, Renvoisé A, Fournier PE, Marié JL, Davoust B, et al. Strikes, flooding, rats, and leptospirosis in Marseille, France. Int J Infect Dis. Oct 2011;15(10):e710-5. 
  6. Wiwanitkit V. Comparison between blood exchange and classical therapy for acute renal failure in Weil's disease: appraisal on Thai reports. Nephrology (Carlton) 2006; 11:481.
  7. Guerrier G, D'Ortenzio E. The Jarisch-Herxheimer reaction in leptospirosis: a systematic review. PLoS One 2013; 8:e59266.
  8. Tunbridge AJ, Dockrell DH, Channer KS, McKendrick MW. A breathless triathlete. Lancet 2002; 359:130.
  9. Suputtamongkol Y, Niwattayakul K, Suttinont C, et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis 2004; 39:1417.
  10. McClain JB, Ballou WR, Harrison SM, Steinweg DL. Doxycycline therapy for leptospirosis. Ann Intern Med 1984; 100:696.
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